Analysis of Immune Cell Infiltration Distribution and Prognostic Value in Obstructive Colorectal Cancer

Area of Science:

• Oncology
• Immunology
• Pathology

Background:

• Colorectal cancer (CRC) prognosis is influenced by the tumor immune microenvironment (TIME).
• Intestinal obstruction is a critical factor in CRC presentation and progression.
• The impact of obstruction on TIME and its prognostic significance remains unclear.

Purpose of the Study:

• To investigate how intestinal obstruction affects the TIME in CRC.
• To analyze the prognostic implications of obstruction-induced TIME changes.
• To correlate local immune cell distribution with peripheral immune markers and patient outcomes.

Main Methods:

• Quantitative immunohistochemistry and digital pathology (QuPath) on 328 CRC resection samples (164 obstructed [OCRC] vs. 164 non-obstructed [NOCRC]).
• Analysis of immune cell densities (CD4+, CD8+, CD20+, CD68+) in central tumor (CT) and invasive margin (IM) compartments.
• Integration of spatial immune data with peripheral blood counts and clinicopathological features; survival analysis (DFS, OS).

Main Results:

• OCRC showed increased lymphocytic infiltration, especially CD8+ T cells in the CT of T4 tumors.
• Obstruction altered immune cell correlations across compartments, with CD68+/CD8+ ratio discriminating obstruction status (AUC for T4 CT = 0.879).
• Peripheral lymphocytopenia was noted in OCRC; T4 OCRC lost correlations between tumor-infiltrating and peripheral immune cells. High CD8+ density in OCRC correlated with worse prognosis, while IM CD68+ macrophages predicted better DFS (HR=0.59).

Conclusions:

• Intestinal obstruction in CRC, particularly T4-stage, creates an immunologically active state altering local immunity and systemic-local crosstalk.
• Obstruction status may refine prognostic stratification and guide therapeutic strategies in CRC.
• Further validation in larger cohorts is necessary to confirm these findings.